There has recently been substantial interest in fibroblast growth factors (FGF's), their biological activity, and their association with certain diseases. Of most interest include FGF-23, a 251-amino acid protein which, in humans, has the amino acid sequence as set forth in SEQ ID NO. 1 and in mice has the amino acid sequence set forth in SEQ ID No. 2. Exemplary of the teachings and publications discussing FGF-23 include Patent Cooperation Treaty International Publication No. WO 01/61007 A2, entitled Fibroblast Growth Factor-23 Molecules and Uses Thereof published on Aug. 23, 2001, and Patent Cooperation Treaty International Publication No. WO 01/66595 A2, entitled Human FGF-23 Gene and Gene Expression Products, published on Sep. 13, 2001, the teachings of both are expressly incorporated herein by reference.
In this regard, currently available data appears to suggest that FGF-23 is either directly or indirectly involved in the regulation of phosphate homeostasis. Moreover, FGF-23 appears to be associated with certain renal phosphate wasting disorders leading to hypophosphatemia, which are among the more significant causes of defective mineralization of bone and growth plate development. For example, patients with autosomal dominant hypophosphatemic rickets (ADHR), a rare genetic disorder, carry one of several FGF-23 mutations that make the protein resistant to proteolytic cleavage. Additionally, tumors that cause oncogenic osteomalacia (OOM) have been shown to over-express FGF-23 mRNA, which is likely attributable to the elevated concentrations of FGF-23 in the blood that consequently causes renal phosphate wasting in this group of patients.
As a result, the measurement of FGF-23, particularly with respect to concentrations in blood circulation, is likely to provide an important indication of the body's ability to regulate phosphate homeostasis, and will further likely serve as an important diagnostic tool for the laboratory evaluation of patients with a variety of different hypophosphatemic disorders. With respect to the latter, it is contemplated that the measurement of human FGF-23 will be particularly important in evaluating disorders such as oncogenic osteomalacia, X-linked hypophosphatemic rickets, and autosomal dominant hypophosphatemic rickets.
Unfortunately, however, there is not yet available an assay capable of qualitatively and quantitatively indicating the presence of FGF-23 within a fluid specimen, much less an immunoassay and assay method that is relatively inexpensive, relatively easy to manufacture, and possesses desired sensitivity and reproducibility necessary for use of such immunoassay and assay method for diagnostic applications.